A major objective of the proposed research will be to explore possible relationships which may exist between calcium in the red blood cell and certain manifestations of a variety of diseases. The diseases to be investigated initially include hereditary spherocytosis, sickle cell anemia, cystic fibrosis and uremia. The propose research has a two-fold purpose: first, to define abnormalities of cellular calcium which may mediate and/or be present in certain manifestations of such diseases; second, to employ normal and abnormal red blood cells as models to explore influences of cellular calcium content and membrane calcium transport on functional properties of human cells. Tests on red blood cells will include measures of deformability, osmotic fragility, autohemolysis, plasma and cellular content of calcium, sodium and potassium, passive and active transport of calcium and sodium, and membrane ATPase activities. From results of such tests in normal cells, disease states and experimentally altered cells, we hope to gain further insight into: 1) control of calcium content of normal human cells, 2) pathophysiology of cellular changes related to abnormalities of cellular calcium, and 3) pharmacological possibilities for selective alteration of cellular calcium or its actions.